1. Field
Disclosed herein is to a device for quantitative and qualitative determination of chemical substances in a liquid flow from a micro-dialysis probe, filter unit, fermenter, cell suspension, chemical reactor, human being, tissue or animal.
The device can also act as a component in equipment for automatic regulation and control of chemical and/or biological processes in fermenters, cell suspensions and chemical reactors.
2. Description of Related Art
The annual world market for liquid chromatography has, from the beginning of the 1960s until today, grown extensively. The market leaders in this area are companies like Pharmacia & Upjohn AB, Applied Biosystems Inc, Bioanalytical Systems, Hitatchi Instruments and Waters Corporation.
In parallel with this development, tools such as micro-dialysis probes, have been produced for in vivo monitoring of patients and animals. Companies that are acting in this area include CMA Microdialys AB (Sweden) and SpectRx Inc (USA).
A third area involving monitoring and control of chemical processes and fermenters is under development. Companies that are active in this area are e.g. Applikon (NL), YSI Inc (USA) and Trace Biotech Ag (Germany). The latter company has. developed a micro-dialysis like device for sampling from a fermentor under sterile conditions.
The common point in the mentioned three areas is that they are all dependent on detection systems, which preferentially are of the type: a flow-through detector. Using different types of flow-through detectors several important chemical substances can be identified and quantified in different types of measuring matrices, exemplified but not limited to fermentation broths, blood, cerebrospinal fluid, urine etc.
Calibration of a flow—through cell is necessary to obtain accurate measuring results in qualitative and quantitative determination of chemical substances in liquid flows from micro-dialysis probes, filter units, fermenters, cell suspensions, chemical reacters, human beings, tissues and animals. The need for calibration originates from the effects on the measuring results from the flow—through cell emanating from either contamination caused by components in the matrix present in the mentioned liquid flow, and/or time dependent fluctuations of the composition of the liquid flow matrix. The latter fluctuations in the liquid flow matrix composition can arise as a result of chemical or biological processes in chemical reactors, fermenters, cell suspensions, and organisms like cells, tissue, human being, animal, plant, micro—organism or funghus.
It is already commonly known that calibration of chemical measuring equipment can be performed with a generally accepted procedure that goes by the name of the standard addition method, i.e. a known amount of the substance that is going to be analyzed is added to the sample solution to be analyzed. The procedure is based on the performance of a first measurement on the pure sample without any addition, followed by one (or more) new measurement (-s) on the sample now containing an addition of a known standard. The amount of the mentioned-substance can then be accurately calculated with mathematical methods.
The problem with this method is that it is cumbersome, time-consuming and demands substantial manual work.
Since 1995 a new type of biosensor technology, SIRE Biosensor, has been developed, which is based on the injection of recognition elements [SE 510 733 (1999), U.S. Pat. No. 6,214,206 (2001) & U.S. Pat. No. 6,706,160 (2004)]. This technology has solved many technological problems usually related to measuring of chemical substances.